Literature DB >> 17607015

Antiinfective applications of toll-like receptor 9 agonists.

Arthur M Krieg1.   

Abstract

The innate immune system detects pathogens by the presence of highly conserved pathogen-expressed molecules, which trigger host immune defenses. Toll-like receptor (TLR) 9 detects unmethylated CpG dinucleotides in bacterial or viral DNA, and can be stimulated for therapeutic applications with synthetic oligodeoxynucleotides containing immune stimulatory "CpG motifs." TLR9 activation induces both innate and adaptive immunity. The TLR9-induced innate immune activation can be applied in the prevention or treatment of infectious diseases, and the adaptive immune-enhancing effects can be harnessed for improving vaccines. This article highlights the current understanding of the mechanism of action of CpG oligodeoxynucleotides, and provides an overview of the preclinical data and early human clinical trial results, applying these TLR9 agonists in the field of infectious diseases.

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Year:  2007        PMID: 17607015      PMCID: PMC2647632          DOI: 10.1513/pats.200701-021AW

Source DB:  PubMed          Journal:  Proc Am Thorac Soc        ISSN: 1546-3222


  87 in total

1.  CpG oligodeoxynucleotides trigger protective and curative Th1 responses in lethal murine leishmaniasis.

Authors:  S Zimmermann; O Egeter; S Hausmann; G B Lipford; M Röcken; H Wagner; K Heeg
Journal:  J Immunol       Date:  1998-04-15       Impact factor: 5.422

2.  CpG DNA is a potent enhancer of specific immunity in mice immunized with recombinant hepatitis B surface antigen.

Authors:  H L Davis; R Weeratna; T J Waldschmidt; L Tygrett; J Schorr; A M Krieg; R Weeranta
Journal:  J Immunol       Date:  1998-01-15       Impact factor: 5.422

3.  Bacterial DNA containing CpG motifs stimulates lymphocyte-dependent protection of mice against lethal infection with intracellular bacteria.

Authors:  K L Elkins; T R Rhinehart-Jones; S Stibitz; J S Conover; D M Klinman
Journal:  J Immunol       Date:  1999-02-15       Impact factor: 5.422

4.  Bacterial DNA causes septic shock.

Authors:  T Sparwasser; T Miethke; G Lipford; K Borschert; H Häcker; K Heeg; H Wagner
Journal:  Nature       Date:  1997-03-27       Impact factor: 49.962

5.  CpG DNA induces sustained IL-12 expression in vivo and resistance to Listeria monocytogenes challenge.

Authors:  A M Krieg; L Love-Homan; A K Yi; J T Harty
Journal:  J Immunol       Date:  1998-09-01       Impact factor: 5.422

6.  CpG motifs in bacterial DNA trigger direct B-cell activation.

Authors:  A M Krieg; A K Yi; S Matson; T J Waldschmidt; G A Bishop; R Teasdale; G A Koretzky; D M Klinman
Journal:  Nature       Date:  1995-04-06       Impact factor: 49.962

7.  CpG DNA induces IgG class switch DNA recombination by activating human B cells through an innate pathway that requires TLR9 and cooperates with IL-10.

Authors:  Bing He; Xugang Qiao; Andrea Cerutti
Journal:  J Immunol       Date:  2004-10-01       Impact factor: 5.422

8.  CpG oligodeoxynucleotides stimulate protective innate immunity against pulmonary Klebsiella infection.

Authors:  Jane C Deng; Thomas A Moore; Michael W Newstead; Xianying Zeng; Arthur M Krieg; Theodore J Standiford
Journal:  J Immunol       Date:  2004-10-15       Impact factor: 5.422

9.  Evaluation of the toxicity of ISIS 2302, a phosphorothioate oligonucleotide, in a 4-week study in CD-1 mice.

Authors:  S P Henry; J Taylor; L Midgley; A A Levin; D J Kornbrust
Journal:  Antisense Nucleic Acid Drug Dev       Date:  1997-10

10.  CpG oligodeoxyribonucleotides rescue mature spleen B cells from spontaneous apoptosis and promote cell cycle entry.

Authors:  A K Yi; M Chang; D W Peckham; A M Krieg; R F Ashman
Journal:  J Immunol       Date:  1998-06-15       Impact factor: 5.422

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  32 in total

Review 1.  Toll-like receptors and B-cell receptors synergize to induce immunoglobulin class-switch DNA recombination: relevance to microbial antibody responses.

Authors:  Egest J Pone; Hong Zan; Jingsong Zhang; Ahmed Al-Qahtani; Zhenming Xu; Paolo Casali
Journal:  Crit Rev Immunol       Date:  2010       Impact factor: 2.214

2.  Immunological priming requires regulatory T cells and IL-10-producing macrophages to accelerate resolution from severe lung inflammation.

Authors:  Neil R Aggarwal; Kenji Tsushima; Yoshiki Eto; Ashutosh Tripathi; Pooja Mandke; Jason R Mock; Brian T Garibaldi; Benjamin D Singer; Venkataramana K Sidhaye; Maureen R Horton; Landon S King; Franco R D'Alessio
Journal:  J Immunol       Date:  2014-03-31       Impact factor: 5.422

Review 3.  Liposome-nucleic acid immunotherapeutics.

Authors:  Steven Dow
Journal:  Expert Opin Drug Deliv       Date:  2008-01       Impact factor: 6.648

Review 4.  Toll-like receptors--sentries in the B-cell response.

Authors:  Isabelle Bekeredjian-Ding; Gaetan Jego
Journal:  Immunology       Date:  2009-11       Impact factor: 7.397

Review 5.  Synthetic oligonucleotides as modulators of inflammation.

Authors:  Dennis Klinman; Hidekazu Shirota; Debra Tross; Takashi Sato; Sven Klaschik
Journal:  J Leukoc Biol       Date:  2008-04-22       Impact factor: 4.962

6.  Rigging Innate Immunity against the Flu.

Authors:  Arthur M Krieg
Journal:  Mol Ther       Date:  2017-08-23       Impact factor: 11.454

7.  Intranasal CpG therapy attenuated experimental fungal asthma in a TLR9-dependent and -independent manner.

Authors:  Hemanth Ramaprakash; Cory M Hogaboam
Journal:  Int Arch Allergy Immunol       Date:  2009-12-16       Impact factor: 2.749

8.  Activation of innate immunity in healthy Macaca mulatta macaques by a single subcutaneous dose of GMP CpG 7909: safety data and interferon-inducible protein-10 kinetics for humans and macaques.

Authors:  V Ann Stewart; Shannon McGrath; Arthur M Krieg; Noelle S Larson; Evelina Angov; Christopher L Smith; Thomas G Brewer; D Gray Heppner
Journal:  Clin Vaccine Immunol       Date:  2007-12-12

9.  A class C CpG toll-like receptor 9 agonist successfully induces robust interferon-alpha production by plasmacytoid dendritic cells from patients chronically infected with hepatitis C.

Authors:  N A Libri; S J Barker; W M C Rosenberg; A E Semper
Journal:  J Viral Hepat       Date:  2009-02-24       Impact factor: 3.728

10.  Unc93B1 biases Toll-like receptor responses to nucleic acid in dendritic cells toward DNA- but against RNA-sensing.

Authors:  Ryutaro Fukui; Shin-ichiroh Saitoh; Fumi Matsumoto; Hiroko Kozuka-Hata; Masaaki Oyama; Koichi Tabeta; Bruce Beutler; Kensuke Miyake
Journal:  J Exp Med       Date:  2009-05-18       Impact factor: 14.307

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